DESCRIPTION (adapted from the application): Although primary prevention strategies have focused on key modifiable risk factors for development and progression of atherosclerosis, such as hypercholesterolemia, coronary heart disease (CHD) remains the leading cause of death in the United States. Many individuals who present with clinical sequelae of atherosclerosis do not have identifiable conventional risk factors for CHD. Epidemiological studies indicate a strong association of plasma tHcy levels with atherosclerosis from childhood to the elderly. A large number of studies have shown plasma tHcy levels to be an independent risk factor for CHD that is easily modifiable with the B-vitamins, folic acid, vitamin B12, and vitamin B6. Plasma tHcy levels rise 25 % after 50 years of age and may partially account for the age-related risk for CHD. The rise in plasma tHcy levels parallel the age-related decrease in serum levels of folate, vitamin B12, and vitamin B6. Elevated they levels result even with these vitamin levels in the normal to low-normal range. Elderly individuals seem to be most susceptible to development of subclinical vitamin deficiencies since dietary intake of these B-vitamins is approximately 50% the Daily Value after 50 years of age. Low serum folate and vitamin B6 levels are significantly associated with CHD risk. Therefore, low B-vitamin status and elevated plasma tHcy levels are important risk factors for atherosclerosis. Evidence, including data from the investigator's laboratory suggests that B-vitamin supplementation can reduce the progression of subclinical atherosclerosis in healthy individuals. Therefore, the investigators propose a multisite, randomized, double-blind, placebo-controlled, 2.5-year, arterial imaging clinical trial with folic acid 5 mg, vitamin B12 2 0.4 mg, and vitamin B6 50 mg versus placebo in healthy men and women >40 years old with LDL-C >130 mg/dL and plasma tHcy >8.5/micromol/L. They will target a cohort of 50% elderly (2-60 years old), 50 % women and 50 % minority subjects. The impact of B-vitamins on the progression of subclinical atherosclerosis will be noninvasively quantitated across several vascular beds with computer image processed B-mode ultrasonograms of carotid artery intima-media thickness and EBCT of the coronary arteries and abdominal aorta. B-vitamin supplementation may provide a promising approach for reducing the progression of atherosclerosis since it is natural, inexpensive, highly tolerable, and safe.